Silylium-Catalyzed Regio- and Stereoselective Carbosilylation of Ynamides with Allylic Trimethylsilanes

The regio- and stereoselective carbosilylation of tosylynamides with allylic trimethylsilanes takes place under mild conditions in the presence of catalytic TMSNTf2 or HNTf2 to give (Z)-α-allyl-β-trimethylsilylenamides with good yields. Theoretical calculations show the activation of the C–C triple bond of the ynamides by the trimethylsilylium ion and formation of a β-trimethylsilylketenimonium cation. Further transformations of the products demonstrate the synthetic utility of this reaction.

S ilylium ion has been consolidated in the past two decades as a potent catalyst in organic synthesis. 1 Its strong Lewis acid character is reflected in its high affinity not only to σbut also to π-bases. This makes silylium ion a simpler and more sustainable alternative to catalytic metal salts or transition metal complexes for the activation of C−C multiple bonds. Since the pioneering work of Lambert et al., employing 1,1disubstituted alkenes, 2 several examples of silylium-catalyzed hydro-3−6 and carbosilylation 7 of C−C double bonds have appeared. However, there are few precedents related to the activation of triple C−C bonds with silylium ion. 8 In this context, Kawashima et al. recently described a silylium catalyzed intermolecular silylation of an arylalkyne 9 to form a β-silyl stabilized vinylcation, that was subsequently intercepted by an intramolecular Friedel−Crafts ring closure.
Exploring new ways for the activation of electron rich triple C−C bonds, ynamides could be good candidates to broad the scope of silylium ion catalysis. The tendency of ynamides to be activated by electrophilic species such as acids and transition metals, 10 and the polarization of their C−C triple bond allow many regioselective reactions. 10,11 Moreover, the 1,2 functionalization of ynamides offers the possibility to obtain functionalized and highly substituted nitrogenated alkenes. 12 Thus, the silylation of these compounds represents an entry to nitrogensubstituted vinylsilanes, 13 of great value in organic synthesis.
Several methods to install a silyl group in one of the carbon atoms of ynamides have been described (Figure 1). Thus, α,βsilylmetalation and subsequent attack of an electrophile to the metal position is the most common method for this purpose ( Figure 1A); for instance, the silylcupration 14 and the Pdcatalyzed silylstannation 15 of ynamides result in α-metalated (Z)-β-silylenamides; alternatively, Pd-catalyzed silylboration leads to β-metalated (Z)-α-silylenamides; 16 finally, α-metalated (E)-β-silylenamides can be obtained from a trans-selective radical silylzincation of ynamides. 17 Apart from the silylmetalation approach, β-silyl-(Z)enamides can also selectively be obtained by hydrosilylation of ynamides using a rhodium complex 18 or tris-(pentafluorophenyl)borane 19 as catalyst; in both cases, the hydride abstraction from the silane by the corresponding catalyst leads to a silylium ion, responsible for the formation of a β-silyl ketenimonium intermediate I ( Figure 1B). Very recently, a palladium catalyzed silylcyanation was described; the reaction proceeds in a stereo-and regioselective way through a β-palladium enamide intermediate II ( Figure 1C). 20 On the other hand, the precedented reactions of allylsilanes with C−C multiple bonds catalyzed by Brønsted or Lewis acids 21−23 and the possibility of self-regeneration of catalytic silylium moved us to choose allylsilane derivatives as carbon nucleophile counterparts for our study on the catalytic carbosilylation of ynamides ( Figure 1D). Therefore, herein we develop a regio-and stereoselective allylsilylation of ynamides, using catalytic silylium ion, an alternative to other species such as metal salts and transition metal complexes.
Our first experiments focused on the reaction between tosylynamide 1a and allyltrimethylsilane 2a in 1,2-dichloroethane (DCE) using a direct silylium ion freshly prepared source like N-trimethylsilyl bis(trifluoromethanesulfonyl)i m i d e , T M S N T f 2 , 2 4 o r a n a c i d l i k e b i s -(trifluoromethanesulfonyl)imide, HNTf 2 , as initiators (10 mol %). 25 To our delight, we obtained in both cases the corresponding allylsilylated enamide 3a, in 50% and 35% yield, respectively, with complete regio-and stereoselectivity ( Table  1, entries 1 and 2).
We employed also trimethylsilyl trifluoromethanesulfonate, TMSOTf, as initiator in the same reaction conditions, but in this case, we observed only decomposition of the reagents (Table 1, entry 3). Then, the yields were improved by increasing the ratio of allylsilane 2a to 4-fold excess (Table 1, entries 4,5); additionally, we observed that lowing the initiator loading to 5 mol % did not seem to affect the efficiency of the reaction (Table 1, entries 6 and 7). Furthermore, comparable yields were obtained with other halogenated solvents such as dichloromethane (Table 1, entry 8); however, the yields were significantly lower with diethyl ether or toluene (Table 1 entries 9 and 10), or simply the reaction did not afford any product when using THF or acetonitrile (Table 1, entries 11 and 12). Finally, the reaction was scaled-up to 2 mmol employing 5 mol % HNTf 2 with an improved yield of 71% (Table 1, entry 7).
With the optimized conditions in hand, we examined the scope of the reaction. We employed either TMSNTf 2 (method A) or HNTf 2 (method B) as initiators with different β-aryl-Nmethyl-N-tosylynamides 1 and allylsilane 2a (Scheme 1).
To get some insight into the reaction mechanism, we performed computational studies at the PCM-M05-2X/6-31G*//M05-2X/6-31G* level. 26 Starting from tosylynamide 1a and TMSNTf 2 , the molecular geometry was fully optimized without any molecular symmetry constraint, leading to structure A (Figure 2), a coordination minimum that placed the Si−C Ph distance at 4.065 Å, keeping the Si−N bond distance at 1.895 Å. Subsequently, the approach between Si and C Ph (Si−C Ph distance = 2.195 Å) induces an elongation  As also shown in Figure 2, the anti-approximation of allyltrimethylsilane 2a to B gave the coordination minimum C anti (+0.4 kcal·mol −1 ), with a distance of 4.093 Å between H 2 C � and C N , which is reduced in the transition state TS2 anti (+8.8 kcal·mol −1 ) to 2.048 Å. TS2 anti led to the minimum D anti (−1.2 kcal·mol −1 ), which in fact has a cyclopropyl structure (bond distances: H 2 C−C N = 1.592 Å, HC−C N = 1.565 Å, and H 2 C−HC = 1.464 Å). Finally, the attack of the Tf 2 N − anion on the silicon atom acts as the driving force of the process, leading directly to the coordination minimum E anti (−41.4 kcal·mol −1 ), formed by the allylsilylated enamide 3a and TMSNTf 2 , without any intermediate being located. Likewise, syn-addition from the coordination minimum C syn (+2.1 kcal·mol −1 ) leads to the minimum D syn (−2.9 kcal·mol −1 ) through the transition state TS2 syn (+13.6 kcal·mol −1 ), which shows a distance of 2.300 Å between H 2 C � and C N . The difference in the energy barriers to reach TS2 anti or TS2 syn (4.8 kcal·mol −1 ) could be explained by the β-silicon effect, 19 which places the bond angles in B at 107°(Si−C Ph −C N ) and 131°(Ph−C Ph −C N ), which avoid synapproximation and allow us to explain the experimentally found stereoselectivity. 26 According to our calculations, the overall process would start from the reaction of 1a with TMSNTf 2 and formation of a βsilyl ketenimonium intermediate B and the Tf 2 N − anion. Intermediate B would receive nucleophilic anti-attack of the C−C double bond of the allylic silane 2a to give the intermediate D anti . The subsequent attack of the Tf 2 N − anion on the silicon atom leads to β-silylenamide 3a and TMSNTf 2 , which closes the catalytic cycle ( Figure 2).
Finally, to illustrate the synthetic possibilities of enamides 3, we carried out several transformations (Scheme 3). Thus, the reaction of β-silylenamide 3o with a fluoride source, such as tetrabutylammonium fluoride, led to the desilylated enamide 4 (86%) or, alternatively, the coupling product 5 (72%) if the reaction was performed in the presence of 4-bromobenzaldehyde (Scheme 3). The allyl group can also intervene in other transformations; thus, the presence of a catalytic amount of a Brønsted acid (HNTf 2 , 1 mol %) gave the 1,2-dihydronaphthalene derivative 6 (65%) because of an intramolecular aromatic electrophilic substitution of the carbocation intermediate formed by previous protonation of the 2-phenylallyl substituent (Scheme 3).
In summary, we have described a regio-and stereoselective carbosilylation of tosylynamides 1 catalyzed by silylium ion. The reaction uses different allylsilanes 2 as the source of the   The data underlying this study are available in the published article and its online Supporting Information.

* sı Supporting Information
The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.orglett.3c00221. Experimental details, materials and methods, characterization data, NMR spectra for all compounds, X-ray diffraction experiments and computational studies data (PDF)